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Improved analysis of genetic testing could lead to more accurate diagnosis of inherited conditions

18 August 2016

A groundbreaking study, led by experts from Royal Brompton Hospital, Imperial College London and the University of Oxford, has discovered better methods to interpret the significance of gene mutations in patients who are tested for genetic conditions. The findings mean that, in future, more diagnoses could be made through genetic testing.  


In the study, which has been published in Genetics in Medicine, researchers compared genetic data from nearly 8,000 patients who have the heart condition cardiomyopathy, with more than 60,000 reference samples from the general population. The aim was to reassess the role that variants (changes) in different genes play in causing the condition, which is a disease of the heart muscle that reduces its ability to pump blood around the body. It affects around 1 in 500 people in the UK.


The cardiomyopathy data set, from the Oxford Molecular Genetics Laboratory and the Laboratory of Molecular Medicine, Partners HealthCare in Boston, USA, is the biggest ever analysed. Researchers compared this with a large volume of raw genetic data from the general population, available from a new database known as ExAC, which was compiled by an international consortium led by the MacArthur Lab in the USA.


Rare variants in genes that are typically associated with dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC), were examined.


The analysis found that only eight out of 48 genes previously implicated in DCM, and two thirds of genes that are regularly screened for HCM, were much more common among the cardiomyopathy patients. This means they are more likely to be disease-causing and therefore most relevant for genetic testing. As a result, clinical scientists can take a more targeted approach to diagnosing these illnesses and can be more confident in providing a positive diagnosis if one of these gene variants is found.


Researcher Roddy Walsh, from the NIHR Royal Brompton Cardiovascular Biomedical Research Unit and a lead author of the paper, said:

“This study has major implications for other diseases with strong genetic components as researchers can apply the same techniques to other studies using the ExAC database. The huge reference data set gives us an unprecedented understanding of gene variation in a normal population, while the large collection of data from cardiomyopathy patients has allowed us to make new insights into the disease.


“Overall, the database has found higher levels of gene variants in the general population than previously thought, but many of these do not cause disease. So it is about knowing what is significant and what isn’t, and communicating that to clinicians so they know how best to interpret genetic tests.”


Experts at Royal Brompton & Harefield NHS Foundation Trust run a comprehensive inherited cardiovascular conditions service which diagnoses and treats patients with cardiomyopathy, as well as other inherited heart conditions such as aortopathy and pulmonary hypertension. These services cover adults, children and fetal life. Patients can be seen separately or in a family clinic and are offered genetic testing to assess if other family members are at risk.


Find out more about our inherited cardiovascular conditions service.

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